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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme inhibitors suppress plasma concentrations of the sodium retaining hormones angiotensin II and aldosterone. This action should potentiate the natriuretic and diuretic effects of loop diuretics. Some studies indicate, however, that the introduction of angiotensin-converting enzyme inhibitors for the treatment of cardiac failure is associated with transient weight gain and the development of oedema. We have compared the natriuretic and diuretic response to intravenous frusemide 40 mg alone with the natriuretic and diuretic response to intravenous frusemide 40 mg following the administration of a single dose of captopril in 12 supine male patients with stable chronic cardiac failure. Captopril lowered the 4 h diuretic response to frusemide from 1160 (60) to 685 (77) ml (P less than 0.05) and the natriuretic response from 120 (9.6) to 68 (11.7) mmol (P less than 0.05). Creatinine clearance fell after captopril from 91 (7.2) to 57 (7.7) ml min-1 (P less than 0.05). Systolic and diastolic blood pressures were lower after the administration of captopril but these changes were not significant. Plasma renin activity rose from 3.8 (1.04) to 12.34 (2.94) ng ml h-1 (P less than 0.05) and plasma angiotensin II was reduced from 24.9 (5.05) to 8.14 (1.8) pg ml-1 (P less than 0.05). Plasma aldosterone concentrations were not significantly lower following captopril. Angiotensin-converting enzyme inhibitors cause an acute fall in creatinine clearance which may reduce the effects of loop diuretics and attention must be paid to diuretic dosage when initiating angiotensin-converting enzyme inhibitors for the treatment of cardiac failure.
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PMID:Acute administration of captopril lowers the natriuretic and diuretic response to a loop diuretic in patients with chronic cardiac failure. 191 30

Congestive heart failure (CHF) is characterized by activation of (i) vasopressor and antinatriuretic influences (ii) and by counter-activation of vasodilator natriuretic systems. The former comprise the sympathoadrenal, renin-angiotensin-aldosterone and arginine vasopressin systems, and possibly endothelin and withdrawal of endothelium dependent relaxing factor respectively. The latter include the prostaglandins (PGE-2, PGI-2), dopamine and atrial natriuretic factor. The response of the kidney to chronic heart failure, i.e. vasoconstriction and antinatriuresis, resembles the renal reaction to volume depletion. The adverse renal effects of ACE inhibitors in some patients with advanced congestive heart failure may be explained by lowering of renal perfusion pressure and dependence of glomerular filtration rate on angiotensin II.
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PMID:The kidney in congestive heart failure. 191 36

The renin-angiotensin system originally was thought to be responsible for only renovascular hypertension, but the development and use of various inhibitors of this system have produced much evidence for its participation in many forms of hypertensive disease. Tissue renin-angiotensin system also may play a major role in blood pressure control. Chronic clinical as well as animal use of converting enzyme inhibitors results in levels of angiotensin II that are equivalent to those found in the normotensive state and higher than those found in the very acute phase of treatment. The source of this conversion possibly may be due to enzymes unrelated to angiotensin converting enzyme. One such enzyme is a very highly specific serine protease isolated from human cardiac tissue. This enzyme exists in human ventricular tissue at levels four to five times that of angiotensin converting enzyme. During chronic treatment of patients with heart failure, angiotensin I levels become high, and heart tissue levels of angiotensin II may become elevated because of the conversion to angiotensin II by this serine protease. This conversion in turn may possibly increase inotropy of the heart, whereas the peripheral resistance remains low because of the reduction of angiotensin II in the circulation.
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PMID:Angiotensin I and II. Some early observations made at the Cleveland Clinic Foundation and recent discoveries relative to angiotensin II formation in human heart. 193 74

Angiotensin converting enzyme inhibitor therapy decreases the production of the vasoconstrictive angiotensin II and reduces the degradation of certain kinines of vasodilatator action. Of captopril, enalapril, and lysinopril marketed abroad, only captopril of shorter action is available in Hungary. Angiotensin converting enzyme inhibitors are new means for the therapy of hypertension and congestive heart failure. Captopril seems to be effective at an early stage of heart failure. It slows down or even inhibits the progression of heart failure. New aspects of therapy have been revealed. It may be successfully used in angina pectoris, for the prevention of reperfusion arrhythmias accompanying myocardial infarction, for the treatment of renoparenchimal renal diseases, diabetic nephropathy. The side-effects, interactions, and dosage of angiotensin converting enzyme inhibitors have also been discussed.
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PMID:Angiotensin converting enzyme inhibitor therapy. 194 79

ACE inhibition may be useful in several manifestations of ischaemic heart disease, such as heart failure due to ischaemic cardiomyopathy. Recent evidence suggests that these effects may also be present in normotensive patients with ischaemic heart disease without heart failure. Theoretically, converting-enzyme inhibition, through coronary and systemic vasodilating effects and negative inotropic properties, should have a favourable effect on the myocardial oxygen supply/demand ratio and, hence, affect the incidence and severity of myocardial ischaemia. It is doubtful, however, whether these cardiac and extracardiac properties of ACE inhibitors really underlie its potential antiischaemic effects, at least in the average patient with ischaemic heart disease without concomitant heart failure and hypertension. Recent animal and human studies indicate that converting-enzyme inhibitors may modulate myocardial ischaemia by reducing ischaemia-induced circulating neurohumoral activation. It has been shown that, depending on the severity of ischaemia, the circulating renin-angiotensin system may become activated together with an increase in circulating catecholamine levels. ACE inhibition suppresses this neuroendocrine stimulation during ischaemia and modulates subsequent systemic and, presumably, also coronary vasoconstriction. In addition to these effects on circulating neurohormones, ACE inhibition could affect myocardial ischaemia through a number of local actions, e.g. modulation of tissue (cardiac) angiotensin II formation and bradykinin breakdown, stimulation of prostaglandin synthesis and, in the use of sulphydryl compounds, by affecting EDRF formation. Whether ACE inhibitors have clear antiischaemic effects in all clinical conditions is uncertain. Their efficacy to limit exercise-induced ischaemia has been questioned. In contrast, pacing-induced ischaemia in patients at rest is clearly prevented by ACE inhibition. This differential effect may be related to a more pronounced difference in circulating neurohormones during exercise per se. It also suggests that ACE inhibitors may be particularly useful as (additional) antiischaemic therapy in patients with angina at rest, e.g. unstable angina and the acute phase of myocardial infarction.
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PMID:Neurohumoral activation during acute myocardial ischaemia. Effects of ACE inhibition. 197 98

The sympathetic activity in cardiac failure is elevated by excitatory afferents from underperfused muscle and from chemoreceptors, and by attenuated inhibitory control via arterial and cardiopulmonary baroreceptors. Together with renal hypotension, the sympathetic activity activates the renin-angiotensin-system, which in turn enhances sympathetic activity. Together, both systems induce a vicious cycle of further cardiac overload by vasoconstriction, volume retention, and formation of edemas, while beta-adrenergic responsiveness of the heart is depressed. The glomerular filtration rate in the kidney is preserved by efferent arteriolar constriction in the face of reduced renal perfusion. Since circulating angiotensins are preferentially formed by angiotensin-forming systems in the tissues, one has to assume strong local effects of angiotensin II at the site of its synthesis. These local effects cannot exactly be quantified from parameters of the circulating RAS. In the heart, myocardial stretch and neuroendocrine activity (via myocardial angiotensin- and alpha 1-receptors) induce a dedifferentiating growth of cardiocytes. This results in an improved economy of myocardial contraction, but also in delayed relaxation with the risk of Ca(++)-overload and generation of arrhythmias by late after-depolarizations. Probably, enhanced intracardiac formation of angiotensin contributes to these dangerous changes.
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PMID:[Pathophysiology of cardiorenal regulatory mechanisms in heart failure]. 202 37

The role of ACE-inhibition for the treatment of congestive heart failure has been established over the last decade. In patients with moderate and severe congestive heart failure long-term beneficial effects on symptoms may be achieved in 60-70%. Mortality is significantly improved in patients with congestive heart failure functional class NYHA IV. Therefore, ACE-inhibitors are superior to other vasodilators. Hypotension represents an important side effect of ACE-inhibitors. It is predominantly due to either inhibition of systemic and/or local angiotensin II formation or to reduce degradation of bradykinin. If the activity of the renin-angiotensin system is stimulated, as in severe congestive heart failure and/or by diuretic pretreatment, the risk for the occurrence of hypotension is therefore increased. With respect to these risk factors, small doses of ACE-inhibitors should be administered initially, e.g. captopril 6.25 mg or enalapril, 2.5 mg. Recently, two large trials demonstrated the safety of enalapril, a long-acting ACE-inhibitor, regarding the occurrence of hypotension in patients with congestive heart failure. The overall incidence of hypotension is about 2-4% in mild to moderate and about 5-8% in severe heart failure. Reduction of the dosage of the ACE-inhibitor or the diuretic drug usually results in normalization of blood pressure, allowing continuation of therapy with ACE-inhibitors.
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PMID:[Side effects of vasodilator therapy in heart failure: risk of hypotension with ACE inhibitors]. 202 38

The evolution of our understanding of the pathogenesis and therapy of heart failure can be described in terms of three paradigms that have also proven useful in describing the development of knowledge of cardiovascular regulation and the actions of angiotensin II. Organ physiology, the first paradigm, viewed the variable performance of the heart in terms of length-dependent changes in myocardial contractile function (Starling's Law), and angiotensin II as a pressor factor that elevated blood pressure. This paradigm focused treatment of heart failure on the major circulatory abnormalities: salt and water retention and vasoconstriction. According to the second paradigm, cell biochemistry, regulation of cardiac performance reflected altered calcium fluxes and changing myocardial contractility, and the clinical effects of angiotensin II as arising from altered calcium fluxes involved in the control of smooth muscle tension. Following this second paradigm, treatment of heart failure focused on powerful inotropic agents designed to increase myocardial contractility. The third paradigm, gene expression (molecular biology) describes what is probably the most primitive, and almost certainly the most complex of these regulatory mechanisms. Altered gene expression explains long-term regulation of cardiac performance in terms of adaptive changes in the architecture and composition of the heart, and key effects of angiotensin II as arising from increased protein synthesis and promotion of cell growth. In the case of heart failure, this third paradigm may explain the accelerated deterioration of the hypertrophied, failing heart as being due to altered myocardial cell growth composition. While the useful life of the normal human heart appears to be at least 80-90 years, overload-induced hypertrophy may reduce the heart's life span to about 5 years. This unwelcome consequence of myocardial hypertrophy may arise from the expression of fetal isoforms of key muscle proteins, a hypothesis that is supported by evidence that deterioration of the failing heart can be alleviated by the converting enzyme inhibitors which have important effects to inhibit cellular growth.
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PMID:Is heart failure an abnormality of myocardial cell growth? 207 54

An abnormal elevation in collagen concentration or myocardial fibrosis occurs in the hypertrophied left ventricle of the rat with renovascular hypertension (RHT). The structural nature and functional consequences of this fibrosis and the mechanisms involved in its appearance were reviewed for various phases of hypertrophy. Within days after the onset of renal ischemia, type I collagen messenger ribonucleic acid is expressed. An interstitial fibrosis follows, characterized by an increased dimension of existing perimysial fibers and the appearance of fibrillar collagen in spaces previously devoid of collagen, together with a perivascular fibrosis of intramyocardial coronary arteries. These expressions of myocardial fibrosis are associated with an increase in diastolic and systolic myocardial stiffness. Endomyocardial fibrosis serves to further increase diastolic stiffness while myocytes encircled by fibrillar collagen become atrophic. Each of these consequences of myocardial fibrosis reduce myocyte length-dependent force generation. At 32 weeks of RHT there is an obvious diastolic and systolic dysfunction of the ventricle together with heart failure that includes ventricular dilatation, wall thinning and reduced ejection fraction. The mechanisms involved in mediating fibrosis in RHT appear to be multiple. Myocyte necrosis and fibroblast proliferation have been associated with elevated circulating angiotensin II. Necrosis in RHT was not seen with captopril pretreatment or in the hypertension and hypertrophy that accompanied infrarenal aorta banding. An alteration in coronary artery permeability may be responsible for the perivascular fibrosis that is not seen with captopril pretreatment. Thus in RHT, the hemodynamic status of the ventricle determines myocyte hypertrophy while the elevation in circulating angiotensin II is responsible for the remodeling of nonmyocyte compartments, including the appearance of myocardial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial fibrosis and pathologic hypertrophy in the rat with renovascular hypertension. 213 51

Cardiac hypertrophy is characterized by marked abnormalities in the contraction/relaxation pattern of the heart. For example, delayed relaxation is a prominent feature, impairing ventricular filling and coronary flow. In intact heart preparations the relative contribution of fibrosis and of the myocardial cell itself to these abnormalities cannot be correctly assessed. Biochemical studies on the mechanisms of impaired contraction and relaxation and hypertensive heart failure are hampered by the fact that 75% of all heart cells are non-myocytes. We therefore established the model of the isolated calcium-tolerant, adult rat cardiomyocyte as a new approach to the investigation of these problems. Contractility was measured using a videomicroscope system with high time resolution (1 ms). Angiotensin II induced a marked relaxation delay in the cardiomyocyte from normotensive rats and showed a moderate positive inotropic effect, whereas isoproterenol had a strong positive inotropic effect but accelerated relaxation. Therefore, angiotensin II is capable of inducing a relaxation delay even in the absence of coronary ischaemia or hypertension. These first results show that the isolated cardiomyocyte model may be a useful approach to investigating the mechanisms of hypertensive heart disease.
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PMID:Isolated myocardial cells: a new tool for the investigation of hypertensive heart disease. 214 54


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